tbuckley/cabot-search huggingface dataset:
Errors in Text and Table of Study on Mood-Linked Changes in Dysfunctional Thinking Among Patients With Depression
Authors: Zindel V. Segal
Journal: JAMA Psychiatry (2022)

To the Editor I write to report errors that occurred in the article “Cognitive Reactivity to Sad Mood Provocation and the Prediction of Depressive Relapse,”1 published in Archives of General Psychiatry (now JAMA Psychiatry) in July 2006.
Evaluation of Adjuvant Chemotherapy Survival Outcomes Among Patients With Surgically Resected Pancreatic Carcinoma With Node-Negative Disease After Neoadjuvant Therapy
Authors: Abdulrahman Y. Hammad, Jacob C. Hodges, Samer AlMasri, Alessandro Paniccia, Kenneth K. Lee, Nathan Bahary, Aatur D. Singhi, Susannah G. Ellsworth, Mohammed Aldakkak, Douglas B. Evans, Susan Tsai, Amer Zureikat
Journal: JAMA Surgery (2022)

Neoadjuvant therapy (NAT) is rarely associated with a complete histopathologic response in patients with pancreatic ductal adenocarcinoma (PDAC) but results in downstaging of regional nodal disease. Such nodal downstaging after NAT may have implications for the use of additional adjuvant therapy (AT).
Disparities in the Inclusion of Racial and Ethnic Minority Groups and Older Adults in Prostate Cancer Clinical Trials
Authors: Irbaz Bin Riaz, Mahnoor Islam, Waleed Ikram, Syed Arsalan Ahmed Naqvi, Hamza Maqsood, Yusra Saleem, Anum Riaz, Praful Ravi, Zhen Wang, Syed A. Hussain, Jeremy Lyle Warner, Folakemi T. Odedina, Narjust Duma, Parminder Singh, Kenneth L. Kehl, Sophia C. Kamran, Mohammad Hassan Murad, Adam Landman, Eliezer Van Allen, Alan Haruo Bryce
Journal: JAMA Oncology (2022)

Prostate cancer (PCa) is marked by disparities in clinical outcomes by race, ethnicity, and age. Equitable enrollment in clinical trials is fundamental to promoting health equity.To evaluate disparities in the inclusion of racial and ethnic minority groups and older adults across PCa clinical trials.MEDLINE, Embase, and ClinicalTrials.gov were searched to identify primary trial reports from each database's inception through February 2021. Global incidence in age subgroups and US population-based incidence in racial and ethnic subgroups were acquired from the Global Burden of Disease and Surveillance, Epidemiology, and End Results 21 incidence databases respectively.All phase 2/3 randomized PCa clinical trials were eligible for age disparity analyses. Trials recruiting exclusively from the US were eligible for primary racial and ethnic disparity analyses.This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were pooled using a random-effects model.Enrollment incidence ratios (EIRs), trial proportions (TPs) of participants 65 years or older or members of a racial and ethnic subgroup divided by global incidence in the corresponding age group, or US population-based incidence in the corresponding racial and ethnic subgroup, were calculated. Meta-regression was used to explore associations between trial characteristics and EIRs and trends in EIRs during the past 3 decades.Of 9552 participants among trials reporting race, 954 (10.8%) were African American/Black, 80 (1.5%) were Asian/Pacific Islander, and 8518 (78.5) were White. Of 65 US trials, 45 (69.2%) reported race and only 9 (13.8%) reported data on all 5 US racial categories. Of 286 global trials, 75 (26.2%) reported the enrollment proportion of older adults. Outcomes by race and age were reported in 2 (3.1%) and 41 (15.0%) trials, respectively. Black (EIR, 0.70; 95% CI, 0.59-0.83) and Hispanic (EIR, 0.70; 95% CI, 0.59-0.83) patients were significantly underrepresented in US trials. There was no disparity in older adult representation (TP, 21 143 [71.1%]; EIR, 1.00; 95% CI, 0.95-1.05). The representation of Black patients was lower in larger trials (meta-regression coefficient, -0.06; 95% CI, -0.10 to -0.02; P = .002).The results of this meta-analysis suggest that Black and Hispanic men are underrepresented in trials compared with their share of PCa incidence. The representation of Black patients has consistently remained low during the past 2 decades.
Molecular Typing and Clinical Characteristics of Synchronous Multiple Primary Colorectal Cancer
Authors: Yandong Zhao, Jingjing Wu, Fengyun Pei, Yanxiang Zhang, Shaomei Bai, Lishuo Shi, Xiang Zhang, Jingjiao Ma, Ximeng Zhao, Tonghui Ma, Jianping Wang, Meijin Huang, Xinjuan Fan, Jun Huang
Journal: JAMA Network Open (2022)

Importance Synchronous multiple primary colorectal cancer (sMPCC) is clinically rare, but its incidence has increased over the past decade. However, little is known about the molecular and clinical features of sMPCC, which may differ from those of single primary colorectal cancer (SPCRC). Objective To evaluate the clinical characteristics and pathogenic variations in lesions and the molecular typing of sMPCC. Design, Setting, and Participants From November 2012 to April 2021, patients with colorectal cancer (CRC) treated at the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this cohort study. Follow-up ended on January 31, 2022. Main Outcomes and Measures The primary outcome was mismatch repair (MMR) status of each lesion in all patients examined using immunohistochemistry (IHC). Microsatellite instability (MSI) and tumor mutation burden (TMB) were also calculated. Results A total of 13 276 patients with CRC were enrolled, and 239 patients with sMPCC (mean [SD] age, 63.3 [12.2] years; 173 men [72.4%]) with available clinical data were evaluated. Seventy-eight patients with sMPCC and 94 with SPCRC also underwent next-generation sequencing (NGS)–based molecular testing. The deficient MMR (dMMR)/MSI-H frequencies in sMPCC were significantly higher than those in SPCRC, which was confirmed by both IHC (50 of 239 patients vs 872 of 13 037 patients) and NGS (17 of 78 patients vs 5 of 94 patients). According to the MMR/MSI status of different lesions in patients with sMPCC, they were further divided into 3 subgroups: all dMMR/MSI-H, dMMR/MSI-H and proficient MMR (pMMR)/microsatellite stability (MSS), and all pMMR/MSS. The EGFR and PIK3CA variants were more common, whereas TP53 variants were less prevalent in patients with sMPCC than in those with SPCRC. Moreover, higher tumor mutation burden was associated with higher MSI in patients with sMPCC rather than in those with SPCRC. Conclusions and Relevance In this cohort study of sMPCC, the incidence of dMMR/MSI-H in patients with sMPCC was significantly higher than that in patients with SPCRC. These findings suggest that sMPCC can be classified into 3 subgroups according to the MMR/MSI status of each lesion, which might be applied to guide personalized therapies for better disease management.
Drinking Water Chlorination Impact on Fecal Carriage of Extended-Spectrum Beta-Lactamase-Producing <i>Enterobacteriaceae</i> in Bangladeshi Children in a Double-Blind, Cluster-Randomized Controlled Trial
Authors: Maria Camila Montealegre, Esther E. Greenwood, Lisa Teichmann, Maya L. Nadimpalli, Lea Caduff, Jenna M. Swarthout, Tabea Nydegger, Sonia Sultana, Mohammad Aminul Islam, Val F. Lanza, Stephen P. Luby, Amy J. Pickering, Timothy R. Julian
Journal: Environmental Health Perspectives (2022)
Rethinking the Role of Experimental Philosophy in Bioethics
Authors: Gonzalo Díaz-Cobacho, Ivar R. Hannikainen
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Place of Philosophy in Bioethics Today Additional informationFundingThis work was supported by Fundació Banc Sabadell; Spanish Ministry of Science and Innovation [PID2020-118729RB-I00] and a Spanish Ministry of Science and Innovation grant with reference number PID2020-119791RA-I00.
Bioethicist Position Available: Philosophers Need Not Apply
Authors: John Banja
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Place of Philosophy in Bioethics Today DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
The Disconnection That Wasn’t: Philosophy in Modern Bioethics from a Quantitative Perspective
Authors: Piotr Bystranowski, Vilius Dranseika, Tomasz Żuradzki
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Place of Philosophy in Bioethics Today Additional informationFundingThis work has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. 805498).
Exploring the “Other” Role of Philosophy in Bioethics: The Case of Addressing Moral Distress and Rediscovering Meaning and Purpose
Authors: Allen Alvarez
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Place of Philosophy in Bioethics Today Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
European Association of Urology Guidelines Panel on Renal Cell Carcinoma Update on the New World Health Organization Classification of Kidney Tumours 2022: The Urologist’s Point of View
Authors: Milan Hora, Laurence Albiges, Jens Bedke, Riccardo Campi, Umberto Capitanio, Rachel H. Giles, Börje Ljungberg, Lorenzo Marconi, Tobias Klatte, Alessandro Volpe, Yasmin Abu-Ghanem, Saeed Dabestani, Sergio Fernández-Pello, Fabian Hofmann, Teele Kuusk, Rana Tahbaz, Thomas Powles, Axel Bex, Kiril Trpkov
Journal: European Urology (2022)
Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination
Authors: Na Wang, Minghui Wang, Suren Jeevaratnam, Cassandra Rosenberg, Tadafumi C. Ikezu, Francis Shue, Sydney V. Doss, Alla Alnobani, Yuka A. Martens, Melissa Wren, Yan W. Asmann, Bin Zhang, Guojun Bu, Chia-Chen Liu
Journal: Molecular Neurodegeneration (2022)

Abstract Background Abnormal lipid accumulation has been recognized as a key element of immune dysregulation in microglia whose dysfunction contributes to neurodegenerative diseases. Microglia play essential roles in the clearance of lipid-rich cellular debris upon myelin damage or demyelination, a common pathogenic event in neuronal disorders. Apolipoprotein E (apoE) plays a pivotal role in brain lipid homeostasis; however, the apoE isoform-dependent mechanisms regulating microglial response upon demyelination remain unclear. Methods To determine how apoE isoforms impact microglial response to myelin damage, 2-month-old apoE2-, apoE3-, and apoE4-targeted replacement (TR) mice were fed with normal diet (CTL) or 0.2% cuprizone (CPZ) diet for four weeks to induce demyelination in the brain. To examine the effects on subsequent remyelination, the cuprizone diet was switched back to regular chow for an additional two weeks. After treatment, brains were collected and subjected to immunohistochemical and biochemical analyses to assess the myelination status, microglial responses, and their capacity for myelin debris clearance. Bulk RNA sequencing was performed on the corpus callosum (CC) to address the molecular mechanisms underpinning apoE-mediated microglial activation upon demyelination. Results We demonstrate dramatic isoform-dependent differences in the activation and function of microglia upon cuprizone-induced demyelination. ApoE2 microglia were hyperactive and more efficient in clearing lipid-rich myelin debris, whereas apoE4 microglia displayed a less activated phenotype with reduced clearance efficiency, compared with apoE3 microglia. Transcriptomic profiling revealed that key molecules known to modulate microglial functions had differential expression patterns in an apoE isoform-dependent manner. Importantly, apoE4 microglia had excessive buildup of lipid droplets, consistent with an impairment in lipid metabolism, whereas apoE2 microglia displayed a superior ability to metabolize myelin enriched lipids. Further, apoE2-TR mice had a greater extent of remyelination; whereas remyelination was compromised in apoE4-TR mice. Conclusions Our findings provide critical mechanistic insights into how apoE isoforms differentially regulate microglial function and the maintenance of myelin dynamics, which may inform novel therapeutic avenues for targeting microglial dysfunctions in neurodegenerative diseases.
Metabolic Changes Associated With Cardiomyocyte Dedifferentiation Enable Adult Mammalian Cardiac Regeneration
Authors: Yuan-Yuan Cheng, Zachery Gregorich, Ray P. Prajnamitra, David J. Lundy, Ting-Yun Ma, Yu-Hsuan Huang, Yi-Chan Lee, Shu-Chian Ruan, Jen-Hao Lin, Po-Ju Lin, Chiung-Wen Kuo, Peilin Chen, Yu-Ting Yan, Rong Tian, Timothy J. Kamp, Patrick C.H. Hsieh
Journal: Circulation (2022)

Cardiac regeneration after injury is limited by the low proliferative capacity of adult mammalian cardiomyocytes (CMs). However, certain animals readily regenerate lost myocardium through a process involving dedifferentiation, which unlocks their proliferative capacities.
A Tumor Microenvironment Model of Pancreatic Cancer to Elucidate Responses toward Immunotherapy
Authors: Verena Kast, Ali Nadernezhad, Dagmar Pette, Anastasiia Gabrielyan, Maximilian Fusenig, Kim C. Honselmann, Daniel E. Stange, Carsten Werner, Daniela Loessner
Journal: Advanced Healthcare Materials (2022)

Pancreatic cancer is a devastating malignancy with minimal treatment options. Standard-of-care therapy, including surgery and chemotherapy, is unsatisfactory, and therapies harnessing the immune system have been unsuccessful in clinical trials. Resistance to therapy and disease progression are mediated by the tumor microenvironment, which contains excessive amounts of extracellular matrix and stromal cells, acting as a barrier to drug delivery. There is a lack of preclinical pancreatic cancer models that reconstruct the extracellular, cellular, and biomechanical elements of tumor tissues to assess responses toward immunotherapy. To address this limitation and explore the effects of immunotherapy in combination with chemotherapy, a multicellular 3D cancer model using a star-shaped poly(ethylene glycol)-heparin hydrogel matrix is developed. Human pancreatic cancer cells, cancer-associated fibroblasts, and myeloid cells are grown encapsulated in hydrogels to mimic key components of tumor tissues, and cell responses toward treatment are assessed. Combining the CD11b agonist ADH-503 with anti-PD-1 immunotherapy and chemotherapy leads to a significant reduction in tumor cell viability, proliferation, metabolic activity, immunomodulation, and secretion of immunosuppressive and tumor growth-promoting cytokines.
Impact of community asymptomatic rapid antigen testing on covid-19 related hospital admissions: synthetic control study
Authors: Xingna Zhang, Ben Barr, Mark Green, David Hughes, Matthew Ashton, Dimitrios Charalampopoulos, Marta García-Fiñana, Iain Buchan
Journal: BMJ (2022)

To analyse the impact of voluntary rapid testing for SARS-CoV-2 antigen in Liverpool city on covid-19 related hospital admissions. Synthetic control analysis comparing hospital admissions for small areas in the intervention population with a group of control areas weighted to be similar for past covid-19 related hospital admission rates and sociodemographic factors. Liverpool city, UK, 6 November 2020 to 2 January 2021, under the intervention of Covid-SMART (systematic meaningful asymptomatic repeated testing) voluntary, open access supervised self-testing with lateral flow devices, compared with control areas selected from the rest of England. General population of Liverpool (n=498 042) and a synthetic control population from the rest of England. Weekly covid-19 related hospital admissions for neighbourhoods in England. The introduction of community testing was associated with a 43% (95% confidence interval 29% to 57%) reduction (146 (96 to 192) in total) in covid-19 related hospital admissions in Liverpool compared with the synthetic control population (non-adjacent set of neighbourhoods with aggregate trends in covid-19 hospital admissions similar to Liverpool) for the initial period of intensive testing with military assistance in national lockdown from 6 November to 3 December 2020. A 25% (11% to 35%) reduction (239 (104 to 333) in total) was estimated across the overall intervention period (6 November 2020 to 2 January 2021), involving fewer testing centres, before England's national roll-out of community testing, after adjusting for regional differences in tiers of covid-19 restrictions from 3 December 2020 to 2 January 2021. The city-wide pilot of community based asymptomatic testing for SARS-CoV-2 was associated with substantially reduced covid-19 related hospital admissions. Large scale asymptomatic rapid testing for SARS-CoV-2 could help reduce transmission and prevent hospital admissions.
Recent developments in the immunopathology of <scp>COVID</scp>‐19
Authors: Huan‐ping Zhang, Yuan‐li Sun, Yan‐fen Wang, Duygu Yazici, Dilek Azkur, Ismail Ogulur, Ahmet Kursat Azkur, Zhao‐wei Yang, Xiao‐xue Chen, Ai‐Zhi Zhang, Jia‐qian Hu, Guang‐Hui Liu, Mübeccel Akdis, Cezmi A. Akdis, Ya‐dong Gao
Journal: Allergy (2022)

Abstract There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID‐19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID‐19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID‐19. The efficacy of the COVID‐19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID‐19 vaccines have changed the clinical scenario of COVID‐19. Multisystem inflammatory syndrome in children (MIS‐C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long‐term symptoms of COVID‐19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID‐19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID‐19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID‐19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID‐19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID‐19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS‐CoV‐2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high‐risk groups, the development of MIS‐C and long COVID‐19.
Transient expression of factor VIII and a chronic high-fat diet induces ER stress and late hepatocyte oncogenesis
Authors: Glenn F. Pierce, Aras N. Mattis
Journal: Molecular Therapy (2022)

Liver-directed gene therapy using adeno-associated virus (AAV) for delivery of therapeutic transgenes has posed particular challenges over the past 25 years, and there are no FDA-approved products to date. Reasons include lack of efficacy or toxicity or both, despite acceptable efficacy and toxicology results in animals, including non-human primates. The experience with AAV-mediated gene therapy for hemophilia is a case in point. The clotting factor VIII gene was cloned in 1984, but production of the full-length recombinant protein is challenging.
Spesolimab: First Approval
Authors: Hannah A. Blair
Journal: Drugs (2022)

Spesolimab (spesolimab-sbzo; SPEVIGO®) is an interleukin (IL)-36 receptor antagonist being developed by Boehringer Ingelheim for the treatment of various immune-mediated disorders. In September 2022, spesolimab was approved in the USA for the treatment of generalized pustular psoriasis (GPP) flares in adults. This article summarizes the milestones in the development of spesolimab leading to this first approval for GPP flares.
Early childhood wheezing phenotypes and determinants in a South African birth cohort: longitudinal analysis of the Drakenstein Child Health Study
Authors: Carlyle McCready, Sadia Haider, Francesca Little, Mark P Nicol, Lesley Workman, Diane M Gray, Raquel Granell, Dan J Stein, Adnan Custovic, Heather J Zar
Journal: The Lancet Child & Adolescent Health (2022)

Developmental trajectories of childhood wheezing in low-income and middle-income countries (LMICs) have not been well described. We aimed to derive longitudinal wheeze phenotypes from birth to 5 years in a South African birth cohort and compare those with phenotypes derived from a UK cohort.
Clinical and economic burden of drug-susceptible tuberculosis in Indonesia: national trends 2017–19
Authors: Deni Iskandar, Auliya A Suwantika, Ivan S Pradipta, Maarten J Postma, Job F M van Boven
Journal: The Lancet Global Health (2022)

The global incidence of tuberculosis is decreasing, yet it remains high in Indonesia. The Indonesian National Tuberculosis Program facilitates mandatory notification, which enables early detection and treatment, minimises complications, prevents transmission, and decreases deaths. This study aimed to assess the characteristics, trends, and economic burden of notified drug-susceptible tuberculosis cases registered in this system from 2017 to 2019.We performed a multiyear cross-sectional study focusing on drug-susceptible tuberculosis notified cases, incidence, geographical tuberculosis case distribution, treatment outcomes, and costs in Indonesia using data from Sistem Informasi Tuberkulosis (2017-19). The settings were Indonesian health-care facilities that provide tuberculosis control programmes and services. Eligible patients were those who were diagnosed with drug-susceptible tuberculosis and notified to Sistem Informasi Tuberkulosis.Between 2017 and 2019, notified cases increased from 429 219 to 523 614 individuals, corresponding to an increase in incidence from 167 cases per 100 000 to 196 cases per 100 000. In 2019, more than 250 cases per 100 000 inhabitants were notified in Jakarta, North Sulawesi, Gorontalo, and Papua. Treatment success rate increased from 363 098 (84·60%) of 429 219 in 2017 to 452 966 (86·51%) of 523 614 in 2019, with a relatively stable mortality, changing from 3·15% to 3·05%. HIV status was increasingly confirmed, with unknown status decreasing from 66·21% to 43·68%. The costs of visits and monitoring and drug regimens were relatively stable, with total direct medical costs slightly increasing from US$39·40 to $40·40 per case.Progress was made on drug-susceptible tuberculosis management in Indonesia. However, further intensified efforts, including case-finding, optimising diagnosis, and cost-effective tuberculosis management are required if Indonesia is to achieve the 2025 WHO End Tuberculosis Strategy target incidence of fewer than 55 cases per 100 000 people. These data are an important starting point for understanding drug-susceptible tuberculosis dynamics in Indonesia and optimising its management.Directorate General of Higher Education; Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia.